• 1
    Electrophysiological effects of endothelin-1 (ET-1) were studied in rabbit sinoatrial node (SAN) using conventional microelectrode and whole-cell voltage and current recordings.
  • 2
    In rabbit SAN, RT-PCR detected ETA endothelin receptor mRNA. ET−1 (100 nm) increased the cycle length of action potentials (APs) from 305 ± 15 to 388 ± 25 ms; this effect was antagonised by the ETA receptor-selective antagonist BQ−123 (1 μm). ET-1 increased AP duration (APD50) by 22 %, depolarised the maximum diastolic potential (MDP) from −59 ± 1 to −53 ± 2 mV, shifted the take-off potential by +5 mV and decreased the pacemaker potential (PMP) slope by 15 %. Under exactly the same experimental conditions, ET-1 caused a positive chronotropic effect in guinea-pig SAN with a decrease of 13 % in APD50, a shift of −4 mV in the take-off potential and an increase of 8 % in the PMP slope.
  • 3
    Rabbit SAN exhibited two major cell types, distinguished both by their appearances and by their electrophysiological responses to ET-1. Whereas the spontaneous pacing rate and the PMP slope were similarly decreased by ET-1 (10 nm) in both cell types, ET-1 depolarised MDP from −67 ± 1 to −62 ± 4 mV in spindle-shaped cells but hyperpolarised it from −73 ± 1 to −81 ± 3 mV in rod-shaped cells. ET-1 decreased APD50 by 8 and 52 % and shifted the take-off potential by +5 and −9 mV in spindle- and rod-shaped cells, respectively.
  • 4
    ET-1 decreased the high-threshold calcium current (ICaL) by about 50 % in both cell types, without affecting its voltage dependence, and decreased the delayed rectifier K+ current (IK) with significant shifts (of +4.7 and +14.0 mV in spindle- and rod-shaped cells, respectively) in its voltage dependence. It was exclusively in rod-shaped cells that ET-1 activated a sizeable amount of time-independent inward-rectifying current.
  • 5
    The hyperpolarisation-activated current (If), observed exclusively in spindle-shaped cells, was significantly increased by ET-1 at membrane potentials between −74.7 and −84.7 mV whereas it was significantly decreased at more negative potentials. ET−1 significantly decreased the slope of the current-voltage (I–V) relation of the If tail without changing its half-maximum voltage.
  • 6
    The overall negative chronotropic influence of ET-1 on the whole rabbit SAN is interpreted as resulting from the integration of its different actions on spindle- and rod-shaped SAN cells through electrotonic interaction.